Liu Y, Suchy F J, Silverman J A, Vore M
Department of Pharmacology, University of Kentucky, Lexington 40536, USA.
Am J Physiol. 1997 Jan;272(1 Pt 1):G46-53. doi: 10.1152/ajpgi.1997.272.1.G46.
The taurocholate (TC) maximal secretory rate (SRm) in the isolated perfused liver is increased in postpartum rats and ovariectomized rats treated with ovine prolactin (oPRL). The present studies were designed to characterize the mechanism(s) by which oPRL increases TC transport in the liver. oPRL (300 micrograms/day i.v. for 7 days) increased the SRm 1.6-fold from 185 to 364 nmol.min-1.mg protein-1 in the perfused rat liver and the maximal rate of transport for ATP-dependent transport 1.7-fold from 66 to 109 nmol.min-1.mg protein-1 in canalicular liver plasma membrane (cLPM) vesicles without changing the Michaelis constant (5-6 microM). The oPRL-mediated increases in biliary excretion in the perfused liver and ATP-dependent TC transport in cLPM vesicles were significantly inhibited by cycloheximide treatment (2 mg/kg). oPRL (300 micrograms/day iv for 7 days) increased expression of Ca(2+)-Mg(2+)-ecto-adenosinetriphosphatase mRNA sixfold and increased protein expression two- to threefold, but had no effect on the expression of P-glycoprotein (mdr1b and mdr2) mRNA. Thus the increase in ATP-dependent transport in cLPM vesicles due to oPRL treatment accounts for the increased TC SRm in the perfused liver. The oPRL-mediated increased TC transport may be associated with increased expression of proteins related to bile acid transport.
在产后大鼠以及用羊催乳素（oPRL）处理的去卵巢大鼠中，离体灌注肝脏中牛磺胆酸盐（TC）的最大分泌率（SRm）会升高。本研究旨在阐明oPRL增加肝脏中TC转运的机制。oPRL（静脉注射300微克/天，共7天）使灌注大鼠肝脏的SRm从185纳摩尔·分钟⁻¹·毫克蛋白⁻¹增加了1.6倍，达到364纳摩尔·分钟⁻¹·毫克蛋白⁻¹，并且使胆小管肝细胞膜（cLPM）囊泡中ATP依赖性转运的最大速率从66纳摩尔·分钟⁻¹·毫克蛋白⁻¹增加了1.7倍，达到109纳摩尔·分钟⁻¹·毫克蛋白⁻¹，而米氏常数（5 - 6微摩尔）不变。用环己酰亚胺处理（2毫克/千克）可显著抑制oPRL介导的灌注肝脏胆汁排泄增加以及cLPM囊泡中ATP依赖性TC转运增加。oPRL（静脉注射300微克/天，共7天）使Ca(2 +)-Mg(2 +)-ecto - 腺苷三磷酸酶mRNA的表达增加了六倍，蛋白表达增加了两到三倍，但对P - 糖蛋白（mdr1b和mdr2）mRNA的表达没有影响。因此，oPRL处理导致cLPM囊泡中ATP依赖性转运增加，这解释了灌注肝脏中TC SRm的增加。oPRL介导的TC转运增加可能与胆汁酸转运相关蛋白的表达增加有关。
